St. Luke's Chapel, October 21, 1935.

The parish of St. Luke's was organized by Greenwich Village community members in the fall of 1820. They named the church after St. Luke, the physician, as a reference to the town's use as refuge from the yellow fever epidemics that plagued New York City during the summers. One of the church's founders was Clement Clark Moore, Oriental and Greek Literature scholar, author of "Twas the Night Before Christmas," and real estate developer of Chelsea.

The church building was constructed between 1821 and 1822 on a plot of land donated by Trinity Church. In 1891 St. Luke's would become a chapel of Trinity Church. That relationship lasted through 1976, when St. Luke's once again became an independent parish of the Episcopal Church.

A major fire in 1981destroyed much of the church building, but thought fundraising the structure was restored. Throughout the later 20th century the church became very active in community ministries, working with people with AIDS and at-risk LGBTQ youth.